目的:银屑病关节炎(PsA)是一种复杂的炎症。翻译后修饰几乎影响正常细胞生物学和发病机制的所有方面。本系统综述的目的是收集所有已发表的关于PsA翻译后修饰的证据。主要结局是评估疾病结局与PsA特定翻译后修饰之间的关联。
方法:在Medline进行了系统的电子搜索,PubMed,科克伦,虚拟健康图书馆,和Embase数据库。共识别出587篇文章;删除重复项并扫描后对59篇进行了评估,其中包括47个。进行了描述性分析,根据评估的翻译后修饰类型对结果进行分组。该协议已在PROSPERO数据库中注册。
结果:确定了七个翻译后修饰:瓜氨酸化,氨甲酰化,磷酸化,糖基化,乙酰化,甲基化,和氧化应激。抗瓜氨酸化肽和抗氨基甲酰化蛋白已在类风湿性关节炎中进行了评估。现在有信息表明,这些抗体可能有助于改善PsA的诊断,并且它们可能与更严重的疾病进展(糜烂,多关节受累,和不良的治疗反应)。糖基化与SIRT2和pSTAT3的表达或Th17和细胞因子白介素-22的存在相关的炎症和磷酸化产物增加有关,提示可能的治疗靶标。
结论:翻译后修饰通常在调节PsA的蛋白质功能中起关键作用,并与疾病结局相关。瓜氨酸化,氨甲酰化,磷酸化,糖基化,乙酰化,甲基化,氧化应激与诊断和预后相关。
OBJECTIVE: Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The aim of this systematic review was to collect all published evidence regarding posttranslational modifications in PsA, and the main outcome was to evaluate an association between disease outcomes and specific posttranslational modifications in PsA.
METHODS: A systematic electronic search was performed in Medline, PubMed, Cochrane, Virtual Health Library, and Embase databases. A total of 587 articles were identified; 59 were evaluated after removing duplicates and scanning, of which 47 were included. A descriptive analysis was conducted, with results grouped according to the type of posttranslational modification evaluated. The protocol was registered at the PROSPERO database.
RESULTS: Seven posttranslational modifications were identified: citrullination,
carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress. Anti-citrullinated peptide and anti-carbamylated protein have been evaluated in rheumatoid arthritis. There is now information suggesting that these antibodies may be helpful in improving the diagnosis of PsA and that they may demonstrate a correlation with worse disease progression (erosions, polyarticular involvement, and poor treatment response). Glycosylation was associated with increased inflammation and phosphorylation products related to the expression of SIRT2 and pSTAT3 or the presence of Th17 and cytokine interleukin-22, suggesting a possible therapeutic target.
CONCLUSIONS: Posttranslational modifications often play a key role in modulating protein function in PsA and correlate with disease outcomes. Citrullination,
carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress were identified as associated with diagnosis and prognosis.